Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.

Examining the Relationship Between Screening for Postpartum Depression and Associated Child Health Service Utilization and Costs: A Study Using the All Our Families Cohort and Administrative Data.

INTRODUCTION: Despite a recognized association between maternal postpartum depression (PPD) and adverse child health outcomes, evidence examining the relationship between PPD symptoms and associated child health service utilization and costs remains unclear. In addition, there is a paucity of evidence describing the relationship between early identification of maternal PPD and associated health service utilization and costs for children. This study aims to address this gap by describing the secondary associations of screening for maternal PPD and annual health service utilization and costs for children over their first five years of life. METHODS: Mothers and children enrolled in the prospective All Our Families cohort were linked to provincial administrative data in Alberta, Canada. Multivariable generalized linear models were used to estimate the average annual inpatient, outpatient, physician, and total health service utilization and costs from a public health system perspective for children of mothers screened high risk for PPD, low/moderate risk for PPD, or unscreened. RESULTS: Total mean costs were greatest for children during their first year of life than other years. Those whose mothers were not screened had significantly lower costs compared to those whose mothers were screened low/moderate risk, despite equivalent health service utilization. DISCUSSION: Findings from this study describe the secondary associations of screening for maternal PPD using a public health system perspective. More research is required to fully understand variations in health costs for children across maternal PPD screening categories.

This study describes the relationship between maternal PPD screening status and annual child health service utilization and costs over the first five years of age. Findings from this administrative data study will support decision-makers in understanding the secondary effects associated with maternal PPD screening and inform future cost-effectiveness analyses of PPD screening interventions using a maternal-child health perspective.

A protocol for the formative evaluation of the implementation of patient-reported outcome measures in child and adolescent mental health services as part of a learning health system.

BACKGROUND: Mental health conditions affect one in seven young people and research suggests that current mental health services are not meeting the needs of most children and youth. Learning health systems are an approach to enhancing services through rapid, routinized cycles of continuous learning and improvement. Patient-reported outcome measures provide a key data source for learning health systems. They have also been shown to improve outcomes for patients when integrated into routine clinical care. However, implementing these measures into health systems is a challenging process. This paper describes a protocol for a formative evaluation of the implementation of patient-reported measures in a newly operational child and adolescent mental health centre in Calgary, Canada. The purpose is to optimize the collection and use of patient-reported outcome measures. Our specific objectives are to assess the implementation progress, identify barriers and facilitators to implementation, and explore patient, caregivers and clinician experiences of using these measures in routine clinical care. METHODS: This study is a mixed-methods, formative evaluation using the Consolidated Framework for Implementation Research. Participants include patients and caregivers who have used the centre's services, as well as leadership, clinical and support staff at the centre. Focus groups and semi-structured interviews will be conducted to assess barriers and facilitators to the implementation and sustainability of the use of patient-reported outcome measures, as well as individuals' experiences with using these measures within clinical care. The data generated by the patient-reported measures over the first five months of the centre's operation will be analyzed to understand implementation progress, as well as validity of the chosen measures for the centres' population. DISCUSSION: The findings of this evaluation will help to identify and address the factors that are affecting the successful implementation of patient-reported measures at the centre. They will inform the co-design of strategies to improve implementation with key stakeholders, which include patients, clinical staff, and leadership at the centre. To our knowledge, this is the first study of the implementation of patient-reported outcome measures in child and adolescent mental health services and our findings can be used to enhance future implementation efforts in similar settings.

Cyclometalated Benzimidazole Osmium(II) Complexes with Antiproliferative Activity in Cancer Cells Disrupt Calcium Homeostasis.

We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C^N)(N^N)2]OTf (N^N = 2,2'-bipyridine and dipyrido[3,2-d:2',3'-f]quinoxaline; C^N = deprotonated methyl 1-butyl-2aryl-benzimidazolecarboxylate) with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. The new compounds are highly kinetically inert and absorb a full-wavelength range of visible light. An investigation of the antiproliferative activity of the new compounds has been performed using a panel of human cancer and noncancerous 2D cell monolayer cultures under dark conditions and green light irradiation. The results demonstrate that the new Os(II) complexes are markedly more potent than conventional cisplatin. The promising antiproliferative activity of selected Os(II) complexes was also confirmed using 3D multicellular tumor spheroids, which have the characteristics of solid tumors and can mimic the tumor tissue microenvironment. The mechanism of antiproliferative action of complexes has also been investigated and revealed that the investigated Os(II) complexes activate the endoplasmic reticulum stress pathway in cancer cells and disrupt calcium homeostasis.

Co-building a training programme to facilitate patient, family and community partnership on research grants: A patient-oriented research project.

INTRODUCTION: Patient engagement in patient-oriented research (POR) is described as patients collaborating as active and equal research team members (patient research partners [PRPs]) on the health research projects and activities that matter to them. The Canadian Institutes of Health Research (CIHR), Canada's federal funding agency for health research, asks that patients be included as partners early, often and at as many stages of the health research process as possible. The objective of this POR project was to co-build an interactive, hands-on training programme that could support PRPs in understanding the processes, logistics and roles of CIHR grant funding applications. We also conducted a patient engagement evaluation, capturing the experiences of the PRPs in co-building the training programme. METHODS: This multiphased POR study included a Working Group of seven PRPs with diverse health and health research experiences and two staff members from the Patient Engagement Team. Seven Working Group sessions were held over the 3-month period from June to August 2021. The Working Group worked synchronously (meeting weekly online via Zoom) as well as asynchronously. A patient engagement evaluation was conducted after the conclusion of the Working Group sessions using a validated survey and semi-structured interviews. Survey data were analysed descriptively and interview data were analysed thematically. RESULTS: The Working Group co-built and co-delivered the training programme about the CIHR grant application process for PRPs and researchers in five webinars and workshops. For the evaluation of patient engagement within the Working Group, five out of seven PRPs completed the survey and four participated in interviews. From the survey, most PRPs agreed/strongly agreed to having communication and supports to engage in the Working Group. The main themes identified from the interviews were working together-communication and supports; motivations for joining and staying; challenges to contributing; and impact of the Working Group. CONCLUSION: This training programme supports and builds capacity for PRPs to understand the grant application process and offers ways by which they can highlight the unique experience and contribution they can bring to each project. Our co-build process presents an example and highlights the need for inclusive approaches, flexibility and individual thinking and application. PATIENT OR PUBLIC CONTRIBUTION: The objective of this project was to identify the aspects of the CIHR grant funding application that were elemental to having PRPs join grant funding applications and subsequently funded projects, in more active and meaningful roles, and then to co-build a training programme that could support PRPs to do so. We used the CIHR SPOR Patient Engagement Framework, and included time and trust, in our patient engagement approaches to building a mutually respectful and reciprocal co-learning space. Our Working Group included seven PRPs who contributed to the development of a training programme. We suggest that our patient engagement and partnership approaches, or elements of, could serve as a useful resource for co-building more PRP-centred learning programmes and tools going forward.

Alignment of patient-centredness definitions with real-life patient and clinician experiences: A qualitative study.

INTRODUCTION: Patient-centred care (PCC) has come to the forefront for many institutions, funding agencies and clinicians, and is integrated into care. Does a disconnect in understanding still exist between patients, healthcare organizations and clinicians in what PCC means and how outstanding issues might be addressed? METHODS: We conducted interviews and focus groups with self-reported chronic care patients and clinicians providing care to these patients exploring PCC experiences, expectations and practices. These data were initially analysed using inductive thematic analysis. This paper reports on the findings of a secondary analysis examining the alignment between patients and clinicians on five key predetermined dimensions of PCC. RESULTS: Eighteen patients participated, representing a range of chronic conditions. Thirty-eight clinicians participated. One thousand and three hundred patient and 1800 clinician codes were identified and grouped into 5 main topics with 140 unique themes (patients) and 9 main topics with 54 unique themes (clinicians). A total of 166 quotes (patient = 93, clinician = 73) were identified for this PCC definition alignment analysis. Partial or complete alignment of patient and clinician perspectives was seen on most dimensions. Key disconnects were observed in patient involvement, patient empowerment and clinician-patient communication. Only 18% of patients reported experiencing patient-centred communication, whereas 57% of clinicians reported using patient-focused communication approaches. CONCLUSION: Overall, study patients and clinicians endorse that many PCC elements occur. This study highlights key differences between patients and clinicians, suggesting persistent challenges. Clinician participants relayed their PCC approaches of informing and educating patients; however, patients often perceive these approaches as didactic, role-diminishing and noncollaborative. Collaborative approaches, such as shared decision-making, hold promise to bridge persistent PCC gaps and should be integrated into medical education programmes. PATIENT OR PUBLIC CONTRIBUTION: This project was conceived and executed with a co-design approach wherein patients with chronic conditions who are trained in research (i.e., see descriptions of Patient and Community Engagement Research in the text) were involved in all stages of the research project alongside other researchers on the project team. Healthcare providers were involved as participants and as principal investigators in the project.

Youth engagement in mental health research: A systematic review.

INTRODUCTION: Patient engagement in youth mental health research has the potential to inform research on the interventions, services and policies that will benefit youth. At present, there is little evidence to guide mental health researchers on youth engagement. This systematic review aims to describe the impacts of youth engagement on mental health research and to summarize youth engagement in mental health research. METHODS: We searched the following databases: MEDLINE, EMBASE and PsycINFO, using a combination of subject headings, keywords and synonyms for the concepts 'patient engagement', 'youth' and 'mental health'. Articles that described engaging youth in mental health research were included. Two reviewers performed the study selection. Study characteristics, research activities performed by youth, impacts of youth engagement, challenges, and facilitators to engagement and recommendations for youth engagement described by authors were extracted. Quality appraisal involved determining the level of engagement of youth and the stage(s) of research where youth were involved. RESULTS: The database search returned 2836 citations, 151 full-text articles were screened and 16 articles, representing 14 studies, were selected for inclusion. Youth were involved at nearly all stages of the research cycle, in either advisory or co-production roles. Youth engagement impacts included enhancing relevant research findings, data collection and analysis and dissemination to academic and stakeholder audiences. Both youth and academic researchers reported personal development across many domains. One negative impact reported was the increase in funding and resources needed for engagement. We produced a list of 35 recommendations under the headings of training, youth researcher composition, strategy, expectations, relationships, meeting approaches and engagement conditions. CONCLUSIONS: This study provides an understanding of the impacts and recommendations of youth engagement in mental health research. The findings from this study may encourage researchers to engage youth in their mental health research and support youth engagement in funding applications. PATIENT AND PUBLIC CONTRIBUTION: We consulted three youths with experience being engaged in mental health research about the review findings and the discussion. One youth designed a visual representation of the results and provided feedback on the manuscript. All youth's input informed the way the findings were presented and the focus of the discussion.

Operationalizing the principles of patient engagement through a Patient Advisory Council: Lessons and recommendations.

BACKGROUND: Inclusiveness, Support, Mutual Respect and Co-Build are the four pillars of patient engagement according to the Strategy for Patient-Oriented Research (SPOR). The aim of this manuscript is to describe the operationalization of these principles through the creation of a Patient Advisory Council (PAC) for the research study titled 'Re-Purposing the Ordering of Routine laboratory Tests (RePORT)'. METHODS: Researchers collaborated with the Alberta SPOR SUPPORT Unit (AbSPORU) Patient Engagement Team to create a diverse PAC. Recruitment was intentional and included multiple perspectives and experiences. PAC meetings were held monthly, and patient research partners received support to function as co-chairs of the PAC. Patient research partners were offered training, support and tailored modalities of compensation to actively engage with the PAC. Regular member check-ins occurred through reflexivity and a formal evaluation of PAC member engagement. RESULTS: The PAC included between 9 and 11 patient research partners, principal investigator, research study coordinator, improvement scientist, resident physician and support members from the AbSPORU team. Twelve monthly PAC meetings were held during the first phase of the project. The PAC made course-changing contributions to study design including study objectives, recruitment poster, interview guide and development of codes for thematic analysis. Patient research partners largely felt that their opinions were valued. Diversity in the PAC membership enhanced access to diverse patient participants. Furthermore, support for co-chairs and patient research partner members enabled active engagement in research. In addition, a culture of mutual respect facilitated patient partner engagement, and co-design approaches yielded rich research outputs. CONCLUSIONS: Collaboration between research teams and Patient Engagement Teams can promote effective patient engagement through a PAC. Deliberate and flexible strategies are needed to manage the PAC to create an ecology of Inclusiveness, Support, Mutual Respect, and Co-Build for meaningful patient engagement. PATIENT OR PUBLIC CONTRIBUTION: Patient research partners were involved in the decision to write this manuscript and collaborated equitably in the conception and development of this manuscript, including providing critical feedback. Patient research partners were active members of the PAC and informed the research project design, participant recruitment strategies, data collection and analysis, and will be involved in the implementation and dissemination of results. They are currently involved in the co-development of a patient engagement strategy using a Human-Centered Design process.

Health related quality of life during dialysis modality transitions: a qualitative study.

BACKGROUND: Modality transitions represent a period of significant change that can impact health related quality of life (HRQoL). We explored the HRQoL of adults transitioning to new or different dialysis modalities. METHODS: We recruited eligible adults (≥ 18) transitioning to dialysis from pre-dialysis or undertaking a dialysis modality change between July and September 2017. Nineteen participants (9 incident and 10 prevalent dialysis patients) completed the KDQOL-36 survey at time of transition and three months later. Fifteen participants undertook a semi-structured interview at three months. Qualitative data were thematically analyzed. RESULTS: Four themes and five sub-themes were identified: adapting to new circumstances (tackling change, accepting change), adjusting together, trading off, and challenges of chronicity (the impact of dialysis, living with a complex disease, planning with uncertainty). From the first day of dialysis treatment to the third month on a new dialysis therapy, all five HRQoL domains from the KDQOL-36 (symptoms, effects, burden, overall PCS, and overall MCS) improved in our sample (i.e., those who remained on the modality). CONCLUSIONS: Dialysis transitions negatively impact the HRQoL of people with kidney disease in various ways. Future work should focus on how to best support people during this time.

Uptake of pediatric patient-reported outcome and experience measures and challenges associated with their implementation in Alberta: a mixed-methods study.

BACKGROUND: Implementing Patient-reported Outcome Measures (PROMs) and Patient-reported Experience Measures (PREMs) is an effective way to deliver patient- and family-centered care (PFCC). Although Alberta Health Services (AHS) is Canada's largest and fully integrated health system, PROMs and PREMs are yet to be routinely integrated into the pediatric healthcare system. This study addresses this gap by investigating the current uptake, barriers, and enablers for integrating PROMs and PREMs in Alberta's pediatric healthcare system. METHODS: Pediatric clinicians and academic researchers with experience using PROMs and PREMs were invited to complete a quantitative survey. Additionally, key stakeholders were qualitatively interviewed to understand current challenges in implementing pediatric PROMs and PREMs within AHS. Quantitative data gathered from 22 participants were descriptively analyzed, and qualitative data from 14 participants were thematically analyzed. RESULTS: Participants identified 33 PROMs and 6 PREMs showing diversity in the types of pediatric PROMs and PREMs currently being used in Alberta and their mode of administration. The qualitatively identified challenges were associated with patients, family caregivers, and clinicians. The absence of system-level support, such as integration within electronic medical records, is considered a significant system-level challenge. CONCLUSIONS: The significant variation in the types of PROMs and PREMs used, the rationale for their use, and their mode of administration demonstrate the diverse and sporadic use of these measures in Alberta. These findings highlight the need for province-wide uniform implementation of pediatric PROMs and PREMs in Alberta. Our results could benefit healthcare organizations in developing evidence-based PROM and PREM implementation strategies in pediatrics.

Increasing access to palliative care for patients with advanced cancer of African and Latin American descent: a patient-oriented community-based study protocol.

BACKGROUND: Cancer disparities are a major public health concern in Canada, affecting racialized communities of Latin American and African descent, among others. This is evident in lower screening rates, lower access to curative, and palliative-intent treatments, higher rates of late cancer diagnoses and lower survival rates than the general Canadian population. We will develop an Access to Palliative Care Strategy informed by health equity and patient-oriented research principles to accelerate care improvements for patients with advanced cancer of African and Latin American descent. METHODS: This is a community-based participatory research study that will take place in two Canadian provinces. Patients and community members representatives have been engaged as partners in the planning and design of the study. We have formed a patient advisory council (PAC) with patient partners to guide the development of the Access to Palliative Care Strategy for people of African and Latin American descent. We will engage100 participants consisting of advanced cancer patients, families, and community members of African and Latin American descent, and health care providers. We will conduct in-depth interviews to delineate participants' experiences of access to palliative care. We will explore the intersections of race, gender, socioeconomic status, language barriers, and other social categorizations to elucidate their role in diverse access experiences. These findings will inform the development of an action plan to increase access to palliative care that is tailored to our study population. We will then organize conversation series to examine together with community partners and healthcare providers the appropriateness, effectiveness, risks, requirements, and convenience of the strategy. At the end of the study, we will hold knowledge exchange gatherings to share findings with the community. DISCUSSION: This study will improve our understanding of how patients with advanced cancer from racialized communities in Canada access palliative care. Elements to address gaps in access to palliative care and reduce inequities in these communities will be identified. Based on the study findings a strategy to increase access to palliative care for this population will be developed. This study will inform ways to improve access to palliative care for racialized communities in other parts of Canada and globally.

Proton Pump Inhibitors Versus Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Meta-analysis and Trial Sequential Analysis.

GOALS AND BACKGROUND: Stress ulcer prophylaxis has been shown to lower gastrointestinal bleeding (GIB) rates. Various agents have been studied, and the optimal strategy continues to be contested. This study evaluates the efficacy between proton pump inhibitors (PPIs) and histamine-2-receptor antagonists. Small sample sizes and methodology flaws limited prior studies. STUDY: A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science, and ClinicalTrials.gov for randomized controlled trials reporting the use of PPI and histamine-2-receptor antagonist reporting rates of GIB and standardized intensive care outcomes. Risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CIs). A trial sequential analysis was performed to guard against errors. RESULTS: A total of 14 randomized controlled trials of 28,526 patients with a mean age of 57.83±17.35 years and 30.82% females. In our pooled analysis, PPI outperformed its comparator (RR: 0.68; 95% CI: 0.57-0.82) in clinically significant GIB. PPI re-demonstrated significant reduction in overt GIB (RR: 0.61; 95% CI: 0.39-0.97). No differences between groups was noted toward all-cause mortality (RR: 1.05; 95% CI: 1.00-1.10) or incidence of pneumonia (RR: 1.11; 95% CI: 0.82-1.51). Duration of stay (SMD: 0.07; 95% CI: -0.04-0.17) and ventilator days (SMD: 0.01; 95% CI: -0.01-0.04) were indifferent between the groups. CONCLUSIONS: Among critically ill patients, PPI was associated with reduced clinically significant or overt GIB. No differences in pneumonia were seen with the use of either agent. Trial sequential analysis for clinically significant GIB ruled out the risk for false-positive results, and thereby it is unlikely that future trials will affect our conclusions.

Measurement invariance of the Seattle Angina Questionnaire in coronary artery disease.

PURPOSE: The Seattle Angina Questionnaire (SAQ) is a widely used patient-reported measure of health status in patients with coronary artery disease. Comparisons of SAQ scores amongst population groups and over time rely on the assumption that its factorial structure is invariant. This study evaluates the measurement invariance of the SAQ across different demographic and clinical groups and over time. METHODS: Data were obtained from the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry, a registry of patients who received coronary angiogram in Alberta, Canada. The study cohort consists of adult patients who completed the paper-based version of the 16-item Canadian version of the SAQ (SAQ-CAN) 2 weeks and 1-year post-coronary angiogram between 2009 and 2016. Multi-group confirmatory factor analysis was used to assess configural, weak, strong, and strict measurement invariance across age groups, sex, angina type, treatment, and over time. Model fit was assessed using the comparative fit index and root mean square error of approximation. RESULTS: Of the 8101 patients included in these analysis, 1300 (16.1%) were at least 75 years old, while 1755 (21.7%) were female, 5154 (63.6%) were diagnosed with acute coronary syndrome, 1177 (14.5%) received coronary artery bypass graft treatment, and 3279 had complete data on the SAQ-CAN at both occasions. There was evidence of strict invariance across age, sex, and angina type, and treatment groups, but partial strict invariance was established over time. CONCLUSION: SAQ-CAN can be used to compare the health status of coronary artery disease patients across population groups and over time.

Codesigning person-centred quality indicators with diverse communities: A qualitative patient engagement study.

INTRODUCTION: Effective engagement of underrepresented communities in health research and policy remains a challenge due to barriers that hinder participation. Our study had two objectives: (1) identify themes of person-centred care (PCC) from perspectives of diverse patients/caregivers that would inform the development of person-centred quality indicators (PC-QIs) for evaluating the quality of PCC and initiatives to improve PCC and (2) explore innovative participatory approaches to engage ethnocultural communities in qualitative research. METHODS: Drawing on participatory action research methods, we partnered with a community-based organization to train six 'Community Brokers' from the Chinese, Filipino, South Asian, Latino-Hispanic, East African and Syrian communities, who were engaged throughout the study. We also partnered with the provincial health organization to engage their Patient and Family Advisory, who represented further aspects of diversity. We conducted focus group discussions with patients/caregivers to obtain their perspectives on their values, preferences and needs regarding PCC. We identified themes through our study and engaged provincial stakeholders to prioritize these themes for informing the development of PC-QIs and codesign initiatives for improving PCC. RESULTS: Eight focus groups were conducted with 66 diverse participants. Ethnocultural communities highlighted themes related to access and cost of care, language barriers and culture, while the Patient and Family Advisory emphasized patient and caregiver engagement. Together with provincial stakeholders, initiatives were identified to improve PCC, such as codesigning innovative models of training and evaluation of healthcare providers. CONCLUSION: Incorporating patient and community voices requires addressing issues related to equity and understanding barriers to effective and meaningful engagement. PATIENT OR PUBLIC CONTRIBUTION: Patient and public engagement was central to our research study. This included partnership with a community-based organization, with a broad network of ethnocultural communities, as well as the provincial health service delivery organization, who both facilitated the ongoing engagement of diverse patients/caregiver communities throughout our study including designing the study, recruiting participants, collecting and organizing data, interpreting findings and mobilizing knowledge. Drawing from participatory action research methods, patients and the public were involved in the codesign of the PC-QIs and initiatives to improve PCC in the province based on the findings from our study.

Including the voice of paediatric patients: Cocreation of an engagement game.

BACKGROUND: Engaging patients in health care, research and policy is essential to improving patient-important health outcomes and the quality of care. Although the importance of patient engagement is increasingly acknowledged, clinicians and researchers still find it difficult to engage patients, especially paediatric patients. To facilitate the engagement of children and adolescents in health care, the aim of this project is to develop an engagement game. METHODS: A user-centred design was used to develop a patient engagement game in three steps: (1) identification of important themes for adolescents regarding their illness, treatment and hospital care, (2) evaluation of the draft version of the game and (3) testing usability in clinical practice. Adolescents (12-18 years) were engaged in all steps of the development process through focus groups, interviews or a workshop. These were audio-recorded, transcribed verbatim and analysed in MAXQDA. RESULTS: (1) The important themes for adolescents (N = 15) were included: visiting the hospital, participating, disease and treatment, social environment, feelings, dealing with staff, acceptation, autonomy, disclosure and chronically ill peers. (2) Then, based on these themes, the engagement game was developed and the draft version was evaluated by 13 adolescents. Based on their feedback, changes were made to the game (e.g., adjusting the images and changing the game rules). (3) Regarding usability, the pilot version was evaluated positively. The game helped adolescents to give their opinion. Based on the feedback of adolescents, some last adjustments (e.g., changing colours and adding a game board) were made, which led to the final version of the game, All Voices Count. CONCLUSIONS: Working together with adolescents, All Voices Count, a patient engagement game was developed. This game provides clinicians with a tool that supports shared decision-making to address adolescents' wishes and needs. PATIENT OR PUBLIC CONTRIBUTION: Paediatric patients, clinicians, researchers, youth panel of Fonds NutsOhra and patient associations (Patient Alliance for Rare and Genetic Diseases, Dutch Childhood Cancer Organization) were involved in all phases of the development of the patient engagement game-from writing the project plan to the final version of the game.

Study protocol for Attachment & Child Health (ATTACHTM) program: promoting vulnerable Children's health at scale.

BACKGROUND: Children's exposure to toxic stress (e.g., parental depression, violence, poverty) predicts developmental and physical health problems resulting in health care system burden. Supporting parents to develop parenting skills can buffer the effects of toxic stress, leading to healthier outcomes for those children. Parenting interventions that focus on promoting parental reflective function (RF), i.e., parents' capacity for insight into their child's and their own thoughts, feelings, and mental states, may understand help reduce societal health inequities stemming from childhood stress exposures. The Attachment and Child Health (ATTACHTM) program has been implemented and tested in seven rapid-cycling pilot studies (n = 64) and found to significantly improve parents' RF in the domains of attachment, parenting quality, immune function, and children's cognitive and motor development. The purpose of the study is to conduct an effectiveness-implementation hybrid (EIH) Type II study of ATTACHTM to assess its impacts in naturalistic, real-world settings delivered by community agencies rather than researchers under more controlled conditions. METHODS: The study is comprised of a quantitative pre/post-test quasi-experimental evaluation of the ATTACHTM program, and a qualitative examination of implementation feasibility using thematic analysis via Normalization Process Theory (NPT). We will work with 100 families and their children (birth to 36-months-old). Study outcomes include: the Parent Child Interaction Teaching Scale to assess parent-child interaction; the Parental Reflective Function and Reflective Function Questionnaires to assess RF; and the Ages and Stages Questionnaire - 3rd edition to examine child development, all administered pre-, post-, and 3-month-delayed post-assessment. Blood samples will be collected pre- and post- assessment to assess immune biomarkers. Further, we will conduct one-on-one interviews with study participants, health and social service providers, and administrators (total n = 60) from each collaborating agency, using NPT to explore perceptions and experiences of intervention uptake, the fidelity assessment tool and e-learning training as well as the benefits, barriers, and challenges to ATTACHTM implementation. DISCUSSION: The proposed study will assess effectiveness and implementation to help understand the delivery of ATTACHTM in community agencies. TRIAL REGISTRATION: Name of registry: https://clinicaltrials.gov/. REGISTRATION NUMBER: NCT04853888 . Date of registration: April 22, 2021.

A multi-step approach to developing a health system evaluation framework for community-based health care.

BACKGROUND: Community-based health care (CBHC) is a shift towards healthcare integration and community services closer to home. Variation in system approaches harkens the need for a conceptual framework to evaluate outcomes and impacts. We set out to develop a CBHC-specific evaluation framework in the context of a provincial ministry of health planning process in Canada. METHODS: A multi-step approach was used to develop the CBHC evaluation framework. Modified Delphi informed conceptualization and prioritization of indicators. Formative research identified evaluation framework elements (triple aim, global measures, and impact), health system levels (tiers), and potential CBHC indicators (n = 461). Two Delphi rounds were held. Round 1, panelists independently ranked indicators on CBHC relevance and health system tiering. Results were analyzed by coding agreement/disagreement frequency and central tendency measures. Round 2, a consensus meeting was used to discuss disagreement, identify Tier 1 indicators and concepts, and define indicators not relevant to CBHC (Tier 4). Post-Delphi, indicators and concepts were refined, Tier 1 concepts mapped to the evaluation framework, and indicator narratives developed. Three stakeholder consultations (scientific, government, and public/patient communities) were held for endorsement and recommendation. RESULTS: Round 1 Delphi results showed agreement for 300 and disagreement for 161 indicators. Round 2 consensus resulted in 103 top tier indicators (Tier 1 = 19, Tier 2 = 84), 358 bottom Tier 3 and 4 indicators, non-CBHC measure definitions, and eight Tier 1 indicator concepts-Mortality/Suicide; Quality of Life, and Patient Reported Outcome Measures; Global Patient Reported Experience Measures; Cost of Care, Access to Integrated Primary Care; Avoidable Emergency Department Use; Avoidable Hospitalization; and E-health Penetration. Post Delphi results refined Tier 3 (n = 289) and 4 (n = 69) indicators, and identified 18 Tier 2 and 3 concepts. When mapped to the evaluation framework, Tier 1 concepts showed full coverage across the elements. 'Indicator narratives' depicted systemness and integration for evaluating CBHC. Stakeholder consultations affirmed endorsement of the approach and evaluation framework; refined concepts; and provided key considerations to further operationalize and contextualize indicators, and evaluate CBHC as a health system approach. CONCLUSIONS: This research produced a novel evaluation framework to conceptualize and evaluate CBHC initiatives. The evaluation framework revealed the importance of a health system approach for evaluating CBHC.

Transcriptomic analysis of polyaromatic hydrocarbon degradation by the halophilic fungus Aspergillus sydowii at hypersaline conditions.

Polycyclic aromatic hydrocarbons (PAHs) are among the most persistent xenobiotic compounds, with high toxicity effects. Mycoremediation with halophilic Aspergillus sydowii was used for their removal from a hypersaline medium (1 M NaCl). A. sydowii metabolized PAHs as sole carbon sources, resulting in the removal of up to 90% for both PAHs [benzo [a] pyrene (BaP) and phenanthrene (Phe)] after 10 days. Elimination of Phe and BaP was almost exclusively due to biotransformation and not adsorption by dead mycelium and did not correlate with the activity of lignin modifying enzymes (LME). Transcriptomes of A. sydowii grown on PAHs, or on glucose as control, both at hypersaline conditions, revealed 170 upregulated and 76 downregulated genes. Upregulated genes were related to starvation, cell wall remodelling, degradation and metabolism of xenobiotics, DNA/RNA metabolism, energy generation, signalling and general stress responses. Changes of LME expression levels were not detected, while the chloroperoxidase gene, possibly related to detoxification processes in fungi, was strongly upregulated. We propose that two parallel metabolic pathways (mitochondrial and cytosolic) are involved in degradation and detoxification of PAHs in A. sydowii resulting in intracellular oxidation of PAHs. To the best of our knowledge, this is the most comprehensive transcriptomic analysis on fungal degradation of PAHs.

Incidence of cervical intraepithelial lesions and human papilloma virus infection in female renal transplant recipients.

BACKGROUND: Female renal transplant recipients (RTR) are at high risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer. The aim of this study was to estimate the incidence of cervical intraepithelial lesions (IL) and HPV infection, and their associated factors, in Mexican RTR. METHODS: This is a prospective cohort study conducted between January 2011 and December 2017. Demographic, clinical, and gynecological data were collected using a previously designed questionnaire. Gynecological examination, cervical cytology, and detection of high- and low-risk HPV DNA were undertaken prior to and after the renal transplant (RT). Colposcopically guided biopsies were obtained from patients who presented high grade squamous intraepithelial lesions (HSIL) during the follow-up period. Diagnoses were established according to the Bethesda system. RESULTS: Among 130 RTR, 62 were eligible for our study. The overall incidence of IL was 17.7% (95% CI, 8% to 27%), (11/62 patients), at 25.6 ± 10.7 months post-RT. Nine out of the eleven affected patients had low-grade squamous intraepithelial lesions (81.8%) and only two had HSIL (18.2%). The incidence of HPV infection, determined in a subgroup of 30 RTR, was 53.3% (95% CI, 35% to 71%), (16 out of 30 patients), at 18.3 ± 8.9 months post-RT. High-risk HPV genotypes were present in 62.5% of HPV positive cases (10/16). In 11 patients (36.6%), HPV infection was not associated to IL. CONCLUSIONS: HPV infection and cervical IL are common in the early posttransplant period. Our findings support the need of screening for cervical cancer to detect precancerous changes in RTR and the need of strengthening the knowledge of medical personnel on this issue.

Using implementation science to inform the integration of electronic patient-reported experience measures (ePREMs) into healthcare quality improvement: description of a theory-based application in primary care.

BACKGROUND: Collecting and monitoring the information from patients through patient-reported experience measures (PREMs) about the quality of care they receive is important for tracking changes in healthcare quality, stimulate innovation, and enhance person-centred care. The objective of this theoretical paper is to discuss the use of implementation science theories, models, and frameworks to inform and evaluate the integration of the electronic collection of PREMs (ePREMs) in healthcare quality improvement for primary care in Canada. METHODS: To assess potential knowledge-to-practice gaps in implementing ePREMs in primary care in Alberta, the overarching implementation model that will be used is the Knowledge to Action Cycle. An integrated knowledge translation approach will ensure ongoing engagement of key stakeholders (e.g. primary care providers, patients) throughout the study. ePREM implementation will be informed by the identification of barriers and facilitators to implementation using the Consolidated Framework for Implementation Research (CFIR). The CFIR brings an organizational perspective providing an opportunity to explore the intervention characteristics, the context of implementation, individual factors, and the processes that influence implementation of ePREMs in healthcare. Identified barriers and facilitators to ePREM implementation will be mapped to evidence-based implementation strategies and prioritized by stakeholders. The RE-AIM framework will be used to guide the evaluation of ePREM implementation outcomes after six months of implementation by assessing Reach, Effectiveness, Adoption, Implementation, and Maintenance (sustainability). DISCUSSION: Consultations with stakeholders affirm the importance of using integrated knowledge translation approaches and the need to better understand how to integrate ePREMs in primary care. Using an implementations science approach, this study can provide guidance for mitigating important ePREM implementation challenges and promote the successful uptake and use of ePREMs for quality improvement in healthcare.